Radiosurgery Before Surgery for the Treatment of Brain Metastases

NCT04895592 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 4 other identifiers: STUDY00001896NCI-2021-02761RAD5234-21P30CA138292
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This early phase I trial identifies the side effects of stereotactic radiosurgery before surgery in treating patients with cancer that has spread to the brain (brain metastases). Radiation may stimulate an anti-tumor immune response. Giving stereotactic radiosurgery before surgery may reduce the risk of the cancer coming back after surgery.

Conditions

Metastatic Malignant Neoplasm in the Brain; Metastatic Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events grade 3 or greater

  Evaluated using Common Terminology Criteria for Adverse Events. Tolerability of this regimen will be defined as \< 33% of patients develop grade \> 3 at 4 months. Adverse events will be summarized descriptively using frequencies and percentages.

  At 4 months post-treatment

Secondary Outcomes (4)

• Density of immune niche in brain metastases

  Up to 2 years

• Time to local recurrence (LR)

  From pre-operative stereotactic radiosurgery (SRS) to intracranial progression at the treated site, assessed up to 2 years

• Time to anywhere brain failure (ABF)

  From preoperative SRS to intracranial progression at any site within the brain, assessed up to 2 years

• Overall survival (OS)

  From pre-operative SRS initiation to death, assessed up to 2 years

Study Arms (2)

Arm A (SRS, low dose dexamethasone, surgery)

EXPERIMENTAL

Patients undergo SRS to the brain metastasis for 1-3 fractions over 1-5 days. Patients also receive low dose dexamethasone PO or IV for 2-21 days until the day of surgical resection. Patients then undergo surgical resection.

Drug: Dexamethasone; Procedure: Resection; Radiation: Stereotactic Radiosurgery

Arm B (SRS, high dose dexamethasone, surgery)

EXPERIMENTAL

Patients undergo SRS to the brain metastasis for 1-3 fractions over 1-5 days. Patients also receive high dose dexamethasone PO or IV for 2-21 days until the day of surgical resection. Patients then undergo surgical resection.

Procedure: Resection; Radiation: Stereotactic Radiosurgery

Interventions

Dexamethasone DRUG

Given PO or IV

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm A (SRS, low dose dexamethasone, surgery)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Arm A (SRS, low dose dexamethasone, surgery); Arm B (SRS, high dose dexamethasone, surgery)

Stereotactic Radiosurgery RADIATION

Undergo SRS

Also known as: Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy, Stereotactic Radiotherapy, stereotaxic radiation therapy, stereotaxic radiosurgery

Arm A (SRS, low dose dexamethasone, surgery); Arm B (SRS, high dose dexamethasone, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years
• Prior or suspected diagnosis of malignancy
• Brain metastases visible on contrasted magnetic resonance imaging (MRI) brain
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy \> 12 weeks as determined by the investigator
• Patients must have adequate organ function as determined by Neurosurgery to undergo surgery
• Willingness and ability of the subject to comply with scheduled visits, study procedures, and study restrictions
• Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation
• Patient must have a negative pregnancy test, be actively taking oral contraceptives or have undergone a hysterectomy

You may not qualify if:

• Patients on any immunosuppressive medication other than dexamethasone
• Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Human immunodeficiency virus (HIV)-positive
• Pregnant or nursing women are excluded
• Prior whole brain radiotherapy or SRS to the same site planned for surgery

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Jansen CS, Pagadala MS, Cardenas MA, Prabhu RS, Goyal S, Zhou C, Chappa P, Vo BT, Ye C, Hopkins B, Zhong J, Klie A, Daniels T, Admassu M, Green I, Pfister NT, Neill SG, Switchenko JM, Prokhnevska N, Hoang KB, Torres MA, Logan S, Olson JJ, Nduom EK, Del Balzo L, Patel K, Burri SH, Asher AL, Wilkinson S, Lake R, Kesarwala AH, Higgins KA, Patel P, Dhere V, Sowalsky AG, Carter H, Khan MK, Kissick H, Buchwald ZS. Pre-operative stereotactic radiosurgery and peri-operative dexamethasone for resectable brain metastases: a two-arm pilot study evaluating clinical outcomes and immunological correlates. Nat Commun. 2024 Oct 14;15(1):8854. doi: 10.1038/s41467-024-53034-6.

  PMID: 39402027 DERIVED

MeSH Terms

Conditions

Brain Neoplasms; Neoplasm Metastasis

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Radiosurgery

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Zachary Buchwald, MD, PhD

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: May 20, 2021
• Study Start: July 20, 2021
• Primary Completion: February 19, 2026
• Study Completion (Estimated): February 19, 2027
• Last Updated: March 21, 2025

Record last verified: 2025-03

Locations

US (1)